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. 2022 Apr 17;11(8):1367. doi: 10.3390/cells11081367

Table 3.

Vitamin-based biomarkers for AD.

Ref Study Cohort and Design Analysis Performed Results Cohort of Variation Biomarker/s
Proposed
Glasø et al., 2004 [338] AD (n = 20), HC (n = 18) Analysis on serum and blood ↓ Blood thiamine
↓ Blood TDP
AD Vit B1
dos Santos et al., 2020 [344] AD (n = 60), HC (n = 60) Complete blood count and Vit B12 levels assessment ↓ Vit B12 AD Vit B12
Lanyau-Domínguez et al., 2020 [351] AD (n = 43), MCI (n = 131), HC (n = 250) Spectrophotometry
and high-resolution liquid chromatography on plasma
↓ Vit A and vit C AD Combination of vit A and vit C
Gold et al., 1995 [339] AD (n = 17), n-AD (n = 17) Microbiologic assay on plasma and RBC ↓ Plasma thiamine
-No correlation between RBC thiamine and AD
AD Vit B1
Wang et al., 2018 [340] AD (n = 90), HC (n = 90) HPLC on whole blood samples ↓ TDP Female AD vs. male AD TDP as protective factor for AD
D’Cunha et al., 2019 [341] AD (n = 63), HC (n = 63) ELISA kit to determine APOE4 on serum ↓ Vit B2 dietary intake AD without APOE4 genotype Vit B2 and folate
Dursun et al., 2016 [346] EOAD (n = 22), LOAD (n = 72), MCI (n = 32), HC (n = 70) Chemiluminescent immunoassay on serum ↓ 25(OH)D LOAD ApoEε4 non-carriers Vit D (in ApoEε4 allele non-carriers)
Ouma et al., 2018 [347] AD (mild: n = 41, moderate: n = 35, severe: n = 32), MCI (n = 61), HC (n = 61) Competitive radioimmunoassay on serum ↓ 25(OH)D3 MCI and AD 25(OH)D3
Blasko et al., 2021 [297] Non-converting HC (n = 13), HC converting to MCI (n = 6), HC converting to AD (n = 6), MCI converting to AD (n = 8), MCI converting to HC (n = 8) and stable MCI (n = 7) Competitive immunoassay on serum ↓ Folate MCI–AD converting pt Folate
An et al., 2019 [342] 2533 participants followed for an average of 2.3 y Immunoassay on serum ↑ Folate, vit B6, and vit B12 intake Pt with better cognitive reserve B vitamins and folate
Murdaca et al., 2021 [343] AD (n = 108) Machine learning approach to correlate blood vitamin levels with MMSE score ↓ Vit D and folic acid Pt with lower MMSE score Combination of vit D and folic acid
Baldacci et al., 2020 [345] SMC (n = 316) Aβ-PET (n = 316, at baseline and 2 y follow-up).
Lumbar puncture (n = 40 at baseline).
Immunoassay on plasma (n = 79, at baseline, 1 y and 3 y follow-up)
↓ Vit B12 Pt with higher plasma total Tau levels Vit B12
de Leeuw et al., 2020 [188] SCD (n = 149), MCI (n = 150). Analysis on serum and plasma ↑ 1,25(OH)2D3 SCD 1,25(OH)2D3
Hooshmand et al., 2014 [348] AD (n = 18), MCI (n = 28), SCI (n = 29) Immunoassay on plasma, ELISA on CSF, MRI scans ↑ 25(OH)D3
↑ 25(OH)D3
-Pt with higher CSF Aβ1–42 levels
-Pt with greater brain volumes
Vit D
Al-Amin et al., 2019 [349] MCI (n = 54) Analysis on serum
MRtrix and NBS on MRI scans
↓ 25(OH)D3 Pt with reduction in total hippocampal volume and connection deficit Vit D
Raszewski et al., 2015 [350] AD (n = 33), n-AD (n = 31) HPLC on serum ↓ Vit A and vit E n-AD Combination of vit A and vit E

Abbreviations: AD, Alzheimer’s disease; CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent assay; EOAD, early-onset AD; HC, healthy controls; HPLC, high-performance liquid chromatography; LOAD, late-onset AD; MCI, mild cognitive impairment; n-AD, non-Alzheimer’s dementia; NBS, network-based statistic; pt, patients; RBC, red blood cells; SCD, subjective cognitive decline; SCI, subjective cognitive impairment; SMC, subjective memory complaints; TDP, thiamine diphosphate; y, years; ↓, decrease; ↑, increase.